POSSIBILITIES OF ANTIGEN-SPECIFIC CYTOKINE RELEASE ESSAYS FOR DIFFERENTIAL DIAGNOSIS OF ACTIVE AND LATENT TUBERCULOSIS INFECTION
Introduction: The review examines pathogenetically significant cytokine biomarkers for differentiating latent tuberculosis infection and active tuberculosis.
Purpose: The purpose of this review is to analyze the capabilities of cytokines antigen-specific release assays, in addition to the interferon-gamma (IFN-γ) release assay, for the differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI). The need for such an analysis is determined by the limited capabilities of the IFN-γ antigen-specific release test (IGRA) for the differentiation of LTBI and ATB.
Methods: The review was conducted using electronic databases (Google Scholar, PubMed, Scopus, Cochrane Library) to identify publications exploring the potential of cytokines antigen-specific release assays as a diagnostic tool for the differential diagnosis of LTBI and ATB. The inclusion criteria were: full-text publications assessing the antigen-specific production of one or more cytokines both upon stimulation with "traditional" immunodominant antigens (ESAT-6 and CFP-10) and other MBT antigens, including phase-dependent ones. The exclusion criteria were: publications evaluating the production of only one antigen-specific IFN-γ; articles in which controls were not reliably tested for LTBI; articles analyzing unstimulated cytokine production; articles in which the differentiating potential of the studied cytokines was not revealed.
Results: The most studied cytokines, both individually and in combination, were IFN-γ, tumor necrosis factor-alpha (TNF-α), Interleukin-2 (IL-2), Interferon gamma-induced protein-10 (IP-10), Interleukin-13 (IL-13), Interleukin-10 (IL-10). The differences in the results obtained are apparently related to the use of various laboratory methods for assessing the level of antigen-specific cytokine production (incubation time, reading format, concentration calculation formulas, etc.), genetic characteristics of the studied population, as well as the use of Mycobacterium tuberculosis antigens (MBT) with different immunodominance.
Conclusion: Several cytokines have shown promise as phase-dependent biomarkers for the differential diagnosis of LTBI and ATB. At the same time, the use of a combination of cytokines improves the diagnosis. To identify a reliable phase-dependent cytokine, it is necessary to unify approaches to methods for assessing cytokine production and the complex of stimulating MBT antigens.
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Tarabayeva A., Abilbayeva A. Possibilities of antigen-specific cytokine release essays for differential diagnosis of active and latent tuberculosis infection // Nauka i Zdravookhranenie [Science & Healthcare]. 2022, (Vol.24) 3, pp. 147-158. doi 10.34689/SH.2022.24.3.018Related publications:
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